Current data support the hypothesis that adenosine and adenine nucleotides are modulators of neuronal activity. Adenosine and adenine nucleotides decrease the rate of release of dopamine, noradrenaline, Gamma-aminobutyric acid and acetylcholine. Adenosine has a depressent effect in animals. Purines are localized in the region of their potenital function since ATP is released along with neurotransmitters from numerous nerve endings. The mechanism of action presumably proceeds through interaction with at least three types of adenosine receptors differing in their affinity for adenosine, their localization on the cell membrane, and their regulation of c-AMP levels. We hypothesize that an alteration of adenosine receptor activity due to elevated purine levels in certain diseases, especially during the period of brain development, disturbs neurotransmitter levels in the brain leading to neuropsychiatric disorders, including mental retardation. The decreased dopamine levels in the striatum of Lesch-Nyhan patients is consistent with this hypothesis. The experimental approach outlined to test this hypothesis will involve the injection of pregnant mouse dams with adenosine and non-metabolizable adenosine analogs. Both the level of catecholamines and of adenosine receptors will be determined in specific regions of the brain. The goal of this research is to gain an understanding of neuropsychiatric disorders and to provide a rational approach for the development of chemotherapy to these disorders.